Recent studies suggest that subclinical HSV infection can be classified into two groups: those who have true asymptomatic infection and those, who after appropriate counselling, can be shown to have unrecognized symptomatic genital herpes. Data from our previous HSV studies suggest host factors controlling asymptomatic vs symptomatic reactivation appear to differ. The overall goal of Project I is to define the frequency and natural history of those with true asymptomatic vs unrecognized infection and compare them with those with known symptomatic disease. HSV seropositive patients recruited from high (STD clinic), middle (University of Washington Family Medical Clinic), and low (University Health Service) HSV-2 seroprevalence settings will be followed prospectively over time. Subsets of patients will perform daily home cultures over a 3-4 month period to evaluate the frequency and anatomic sites of asymptomatic shedding and define the association between asymptomatic reactivation and HSV serologic status, i.e. HSV-2 vs HSV-1 and HSV-2. As pilot studies indicate rectal HSV-2 and urinary HSV-1 shedding are more frequent than previously appreciated, asymptomatic shedding from these sites, (in addition to the cervix, vulva and penile area) will be evaluated. Studies using newly developed DNA amplification techniques to detect HSV DNA in prostatic and other genitourinary tissue are proposed. Studies of the transmission of HSV among exposed sexual partners of those with asymptomatic genital herpes will also be conducted. Whether asymptomatic acquisition is more common after contact with an asymptomatic vs symptomatic carries will be explored. The above studies should lead to revised treatment and counselling guidelines for persons with asymptomatic genital herpes.